NOD2 and inflammatory bowel disease: At the same time, evidence is accumulating—from large-scale GWAS [3,5], fine-mapping [5–7], re-sequencing [2,8] and trans-ethnic studies [9,10]–that most (though not all) GWAS signals are driven by causal variants that are themselves common, with evidence supporting alternative rare variant association models (e.g. synthetic association [1]) restricted to a few loci (e.g. NOD2/CARD15 in inflammatory bowel disease [8]).